A phase I/II trial of GW572016 (lapatinib) in recurrent glioblastoma multiforme: clinical outcomes, pharmacokinetics and molecular correlation

Abstract

Lapatinib apparent oral clearance increased by approximately tenfold when given with EIAEDs. In this small sample, EGFRvIII expression and PTEN loss did not predict a favorable subtype. Overall, lapatinib did not show significant activity in GBM patients.

Combined Inhibition of HER1/EGFR and RAC1 Results in a Synergistic Antiproliferative Effect on Established and Primary Cultured Human Glioblastoma Cells

“…However, the use of HER1/EGFR inhibitors targeting the inactive conformation of the receptor should be regarded with caution. So far, two clinical studies have failed to show a clinical benefit of lapatinib in the setting of recurrent glioblastoma (38,40). These results may be partly explained by the fact that mean tumor tissue concentrations of lapatinib were more than 10 times lower than those reported for erlotinib, which has a molecular size that is approximately half of that of lapatinib (38,41).…”

Biomarkers in Glioblastoma multiforme. Evidences from a literature review

“…Studies reporting the prognostic or predictive value of EGFRvIII are listed in Table 1 [8,15,16,[21][22][23][24][25][26][27][28][29][30][31][32][33][34]. We found 17 studies considering 1656 GBM patients overall.…”

“…Nine out of 17 (52.9%) studies (651 patients) reported no prognostic/predictive value of EGFRvIII expression. and of other members of RTK pathway are listed in Table 2 [15, 16,26,28,29,[35][36][37][38][39][40][41][42][43][44][45]. Overall, 16 studies enrolling 1927 patients could be found.…”

Biomarker Discovery, Validation and Clinical Application for Patients Diagnosed with Glioma

“…Unfortunately, the relationship between EGFRvIII and intact PTEN co-expression did not translate to the subsequent prospective phase I/II trials (Brown et al 2008;van den Bent et al 2009). No relationship between aberrations in the RTK core and the EGFR inhibitor, lapatinib (Thiessen et al 2010) or addition of erlotinib with the mTOR inhibitor, sirolimus (Reardon et al 2010) were linked with response.…”